The impact of β-lactamases on the development of novel antimicrobial agents

Current Opinion in Investigational Drugs

Volumn 3, Issue 9, 2002, Pages 1284-1290

  Bush, Karen ^a  

^a JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

Lactamases; Carbapenems; Cephalosporins; Monobactams; MRSA; Penems

Indexed keywords

2 (2 AMINOMETHYL 3 TETRAHYDROFURANYLTHIO) 6 (1 HYDROXYETHYL) 1BETA METHYL 1 CARBAPEN 2 EM 3 CARBOXYLIC ACID; 2 [[[6 (1 HYDROXYETHYL) 2 METHYL 7 OXO 4 THIA 1 AZABICYCLO[3.2.0]HEPT 2 EN 3 YL]METHYL]METHYLAMINO]ACETAMIDE; 3 (4 AMINO 1,1 DIMETHYLBUTYL) 6 (1 HYDROXYETHYL)OXAPENEM 3 CARBOXYLIC ACID; 3 [(6,7 DIHYDRO 5H PYRROLO[1,2 A]IMIDAZOL 6 YL)THIO] 6 (1 HYDROXYETHYL) 4 METHYL 7 OXO 1 AZABICYCLO[3.2.0]HEPT 2 ENE 2 CARBOXYLIC ACID PIVALOYLOXYMETHYL ESTER; 6 (1 HYDROXYETHYL) 4 METHYL 7 OXO 3 (5 OXO 3 PYRROLIDINYLTHIO) 1 AZABICYCLO[3.2.0]HEPT 2 ENE 2 CARBOXYLIC ACID; 6 (1 HYDROXYETHYL) 4 METHYL 7 OXO 3 (5 OXO 3 PYRROLIDINYLTHIO) 1 AZABICYCLO[3.2.0]HEPT 2 ENE 2 CARBOXYLIC ACID PIVALOYLOXYMETHYL ESTER; 6 (1 HYDROXYETHYL) 4 METHYL 7 OXO 3 [1 (2 THIAZOLIN 2 YL) 3 AZETIDINYL] 1 AZABICYCLO[3.2.0]HEPT 2 ENE 2 CARBOXYLIC ACID PIVALOYLOXYMETHYL ESTER; 6 (1 HYDROXYETHYL) 4 METHYL 7 OXO 3 [1 (2 THIAZOLIN 2 YL) 3 AZETIDINYLTHIO] 1 AZABICYCLO[3.2.0]HEPT 2 ENE 2 CARBOXYLIC ACID; 7 [[(2 AMINO 5 CHLORO 4 THIAZOLYL)(HYDROXYIMINO)ACETYL]AMINO] 3 [[3 [[(2 AMINOETHYL)THIO]METHYL] 4 PYRIDINYL]THIO] 8 OXO 5 THIA 1 AZABICYCLO[4.2.0]OCT 2 ENE 2 CARBOXYLIC ACID; 7BETA [2 (5 AMINO 1,2,4 THIADIAZOL 3 YL) 2 ETHOXYIMINOACETAMIDO] 3 [(1 METHYLAMINOPROPYL 1H IMIDAZO[4,5 B]PYRIDINIUM 4 YL)METHYL] 3 CEPHEM 4 CARBOXYLIC ACID; AM 114; ANTIINFECTIVE AGENT; BETA LACTAM; BETA LACTAMASE; BETA LACTAMASE INHIBITOR; BMS 247243; CARBAPENEM DERIVATIVE; CEFALEXIN; CEFTOBIPROLE; CEFTOBIPROLE MEDOCARIL; CEPHALOSPORIN C; CEPHALOSPORIN DERIVATIVE; CILASTATIN; CLOXACILLIN; DU 6681A; FAROPENEM DALOXATE; FROPENEM; IMIPENEM; MEN 11505; MG 2121; MONOBACTAM DERIVATIVE; OCA 983; PENEM DERIVATIVE; PENICILLIN DERIVATIVE; PENICILLIN G; RWJ 442831; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANTIBIOTIC RESISTANCE; ANTIBIOTIC SENSITIVITY; ANTIMICROBIAL ACTIVITY; BACTERIAL INFECTION; BACTERIAL STRAIN; BACTERIUM ISOLATE; CLINICAL TRIAL; COMMUNICABLE DISEASE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG FORMULATION; DRUG HALF LIFE; DRUG HYDROLYSIS; DRUG POTENTIATION; DRUG STABILITY; ENDOCARDITIS; ENZYME INHIBITION; GRAM POSITIVE COCCI; HUMAN; IN VIVO STUDY; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; MINIMUM INHIBITORY CONCENTRATION; NONHUMAN; REVIEW;

ANIMALS; ANTI-BACTERIAL AGENTS; BETA-LACTAMASES; BETA-LACTAMS; HUMANS; TECHNOLOGY, PHARMACEUTICAL;

EID: 0036771257     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (72)

1. Bush K, Mobashery S: How β-lactamases have driven pharmaceutical drug discovery. From mechanistic knowledge to clinical circumvention. In: Resolving the Antibiotic Paradox. Rosen BA, Mobashery S (Eds), Plenum Publishers, NY, USA (1998):71-98. A review describing the role of β-lactamases in the drug discovery process used to identify β-lactam-containing antibacterial agents, including mechanism of action with respect to hydrolysis of β-lactamase substrates and inhibition mechanisms for the β-lactamase inhibitors.
2. Ambler RP, Coulson AFW, Frère J-M, Ghuysen J-M, Joris B, Forsman M, Levesque RC, Tiraby G, Waley SG: A standard numbering scheme for the class A β-lactamases. Biochem J (1991) 276:269-270.
3. Bush K, Jacoby GA, Medeiros AA: A functional classification scheme for β-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother (1995) 39:1211-1233.
4. Bush K: New β-lactamases in Gram-negative bacteria: Diversity and impact on the selection of antimicrobial therapy. Clin Infect Dis (2001) 32:1085-1089.
5. Livermore D, Woodford N: Carbapenemases: A problem in waiting? Curr Opin Microbiol (2000) 3:489-495.
6. Rasmussen BA, Bush K: Carbapenum-hydrolyzing β-lactamases. Antimicrob Agents Chemother (1997) 41:223-232.
7. Kelly JA, Dideberg O, Charlier P, Wery JP, Libert M, Moews PC, Knox JR, Duez C, Fraipoint C, Joris B et al: On the origin of bacterial resistance to penicillin: Comparison of a β-lactamase and a penicillin target. Science (1986) 231:1429-1431.
8. Abraham EP, Chain E: An enzyme from bacteria able to destroy penicillin. Nature (1940) 146:837.
9. Kirby WMN: Extraction of a highly potent penicillin inactivator from penicillin resistant staphylococci. Science (1944) 99:452-453.
10. Barnes JM: Penicillin and Bacillus anthracis. J Path Bact (1947) LIX:113-125.
11. Abraham EP: The β-lactam antibiotics. Sci Am (1981) 244:76-86.
12. Knox R, Smith JT: Antibacterial activity, penicillinase stability and inducing ability of different penicillins. J Gen Microbiol (1962) 28:471-478.
13. Maiti SN, Phillips OA, Micetich RG, Livermore DM: β-Lactamase inhibitors: Agents to overcome bacterial resistance. Curr Med Chem (1998) 5:441-456.
14. Fines M, Leclercq R: New antibiotics in development in the macrolide, lincosamide and streptogramin group. Curr Opin Anti-Infective Invest Drugs (1999) 1:443-452.
15. Tally FP, DeBruin MF: Development of daptomycin for Gram-positive infections. J Antimicrob Chemother (2000) 46:523-526.
16. Pootoolal J, Neu J, Wright GD: Glycopeptide antibiotic resistance. Annu Rev Pharmacol Toxicol (2002) 42:381-408.
17. Pflouffe J: Emerging therapies for serious Gram-positive bacterial infections: A focus on linezolid. Clin Infect Dis (2000) 31(Suppl 4):144-149.
18. LeClercq R: Overcoming antimicrobial resistance: Profile of a new ketolide antibacterial telithromycin. J Antimicrob Chemother (2001) 48(Suppl T1):9-23.
19. Sader HS, Gales AC: Emerging strategies in infectious diseases: New carbapenem and trinem antibacterial agents. Drugs (2001) 61:553-564. A review of carbapenem development, including some of the older agents and their properties.
20. Chenoweth C, Lynch JP III: Antimicrobial resistance: Implications for managing respiratory failure. Curr Opin Pulm Med (1997) 3:159-169.
21. Fish DN, Singletary TJ: Meropenem, a new carbapenem antibiotic. Pharmacotherapy (1997) 17:644-669.
22. Odenholt I: Ertapenem: A new carbapenem. Exp Opin Invest Drugs (2001) 10:1157-1166. A review of preclinical microbiology and pharmacology data on ertapenem, in addition to pharmacokinetic evaluations from clinical trials.
23. Okuda J, Otsuki M, Oh T, Nishino T: In vitro activity of DU-6681a, an active form of the new oral carbapenem compound DZ-2640, in comparison with that of R-95867, faropenem and oral cephalosporins. J Antimicrob Chemother (2000) 46:101-108.
24. Miyazaki S, Hosoyama T, Furuya N, Ishii Y, Matsumoto T, Ohno A, Tateda K, Yamaguchi K: In vitro and in vivo antibacterial activities of L-084, a novel oral carbapenem, against causative organisms of respiratory tract infections. Antimicrob Agents Chemother (2001) 45:203-207. In vitro susceptibility data and efficacy data from murine infection models for a prototypical oral carbapenem and its active metabolite.
25. Kato N, Tanaka K, Kato H, Watanabe K: In vitro activity of R-95867, the active metabolite of a new oral carbapenem, CS-834, against anaerobic bacteria. J Antimicrob Chemother (2000) 45:357-361.
26. Hikida M, Itahashi K, Igarashi A, Shiba T, Kitamura K: In vitro antibacterial activity of LJC 11,036, an active metabolite of L-084, a new oral carbapenem antibiotic with potent antipneumococcal activity. Antimicrob Agents Chemother (1999) 43:2010-2016.
27. Yamaguchi K, Domon H, Miyazaki S, Tateda K, Ohno A, Ishii K, Matsumoto T, Furuya N: In vitro and in vivo antibacterial activities of CS-834 a new oral carbapenem. J Antimicrob Chemother (1998) 42:555-563.
28. Tanaka M, Hohmura M, Nishi T, Sato K, Hayakawa I: Antimicrobial activity of DU-6681a, a parent compound of novel oral carbapenem DZ-2640. Antimicrob Agents Chemother (1997) 41:1260-1268.
29. Fukuoka T, Ohya S, Utsui Y, Domon H, Takenouchi T, Koga T, Masuda N, Kawada H, Kakuta M, Kubota M, Ishii C et al: In vitro and in vivo antibacterial activities of CS-834, a novel oral carbapenem. Antimicrob Agents Chemother (1997) 41:2652-2663.
30. Weiss WJ, Petersen PJ, Jacobus NV, Lin YI, Bitha P, Testa RT: In vitro activities of aminomethyl-substituted analogs of novel tetrahydrofuranyl carbapenems. Antimicrob Agents Chemother (1999) 43:454-459.
31. Yang Y, Testa RT, Bhachech N, Rasmussen BA, Bush K: Biochemical characterization of novel tetrahydrofuranyl 1-β-methylcarbapenems: Stability to hydrolysis by renal dehydropeptidases and bacterial β-lactamases, binding to penicillin binding proteins, and permeability properties. Antimicrob Agents Chemother (1999) 43:2904-2909.
32. Weiss WJ, Mikels SM, Petersen PJ, Jacobus NV, Bitha P, Lin Y-I, Testa RT: In vivo activities of peptidic prodrugs of novel aminomethyl tetrahydrofuranyl-1β-methylcarbapenems. Antimicrob Agents Chemother (1999) 43:460-464.
33. Livermore DM: Interplay of impermeability and chromosomal β-lactamase in imipenem-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother (1992) 36:2046-2048.
34. Tanaka M, Kato K, Hakusui H, Murakami Y, Sato K, Ito Y, Kawamoto K: Pharmacokinetics and safety of ascending single doses of DZ-2640, a new oral carbapenem antibiotic, administered to healthy Japanese subjects. Antimicrob Agents Chemother (2000) 44:578-582.
35. Umemura K, Ikeda Y, Kondo K, Nakashima M, Naganuma H, Hisaoka M, Nishino H, Tajima M: Safety and pharmacokinetics of CS-834, a new oral carbapenem antibiotic, in healthy volunteers. Antimicrob Agents Chemother (1997) 41: 2664-2669.
36. Woodcock JM, Andrews JM, Brenwald NP, Ashny JP, Wise R: The in vitro activity of faropenem, a novel oral penem. J Antimicrob Chemother (1997) 39:35-43.
37. Nishino T, Maeda Y, Ohtsu E, Koizuka S, Nishihara T, Adachi H, Okamoto K, Ishiguro M: Studies on penem antibiotics. II. In vitro activity of SUN5555, a new oral penem. J Antibiot (1989) 42:977-988.
38. Inoue E, Mitsuhashi S: In vitro antibacterial activity and β-lactamase stability of SY5555, a new oral penem antibiotic. Antimicrob Agents Chemother (1994) 38: 1974-1979.
39. Bergan T, Fonseca JD: Comparative antibacterial activity of the penem ALP 201. Chemotherapy (1991) 37:413-419.
40. Sewell D, Barry A, Allen S, Fuchs P, McLaughlin J, Pfaller M: Comparative antimicrobial activities of the penem WY-49605 (SUN5555) against recent clinical isolates from five US medical centers. Antimicro Agents Chemother (1995) 39:1591-1595.
41. Black JA, Moland ES, Chartrand SA, Thomson KS: Activity of faropenem against resistant isolates of Streptococcus pneumoniae. Diagn Microbiol Infect Dis (2001) 41:89-92.
42. Critchley IA, Karlowsky JA, Draghi DC, Jones ME, Thornsberry C, Murfitt K, Sahm DF: Activities of faropenem, an oral β-lactam, against recent US isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Antimicrob Agents Chemother (2002) 46:550-555. Susceptibility data for faropenem compared to activities of agents used for both community-acquired and nosocomial respiratory infections. Isolates were collected from 237 hospitals in the US during 1999.
43. Ferrari L, Altamura M, De Luca M, Ceruti T: MEN 10700, a new penem antibiotic: In vitro antibacterial activity on clinical isolates. Chemotherapy (2002) 48:15-20.
44. Jamieson CE, Lambert PA, Simpson IN: Protection of ceftazidime against class A and class C β-lactamases by oxapenems. ICAAC (2001) 41:Abs F383. Four oxapenems tested as inhibitors of crude β-lactamases from class A, C and D. Synergy data were generated with ceftazidime against 36 organisms producing class A and class C enzymes.
45. Jamieson CE, Lambert PA, Hakenbeck R, Simpson IN: AM-112, a novel oxapenem β-lactamase inhibitor with unexpected synergistic activity with ceftazidime against enterococci, including some vancomycin-resistant isolates. ICAAC (2001):Abs F382.
46. Livermore DM, Tysall L, Warner M, Simpson IN: Activity of oxapenem AM-112 as an antibiotic and as an inhibitor of class A and C β-lactamases. ICAAC (2001):Abs F380.
47. Simpson IN, Di Modugno E, Jabes D, Nicolau D: Oxapenem AM-112: In vivo efficacy alone and in combination with ceftazidime in animal models of infection, involving pathogens producing class A and class C β-lactamases. ICAAC (2001):Abs F385.
48. Kumar S, Pearson AL, Pratt RF: Design, synthesis, and evaluation of α-ketoheterocycles as class C β-lactamase inhibitors. Bioorg Med Chem (2001) 9:2035-2044.
49. Grant EB, Guiadeen D, Baum EZ, Foleno BD, Jin H, Montenegro DA, Nelson EA, Bush K, Hlasta DJ: The synthesis and SAR of rhodanines as novel class C β-lactamase inhibitors. Bioorg Med Chem Lett (2001) 10:2179-2182.
50. Bell JH, Curley K, Pratt RF: Inhibition of serine amidohydrolases by complexes of vanadate with hydroxamic acids. Biochem Biophys Res Commun (2000) 274:732-735.
51. Kaur K, Pratt RF: Mechanism of reaction of acyl phosph(on)ates with the β-lactamase of Enterobacter cloacea P99. Biochemistry (2001) 40:4610-4621.
52. Abou-Khalil A, Beaulieu C, Bernstein N, Besterman J, Bouchain C, Delorme D, Griffin A, Lavoie R, Roby J, Rahil J, Ruel R et al: Sulfonamidomethylphosphonates: Novel non-β-lactam β-lactamase inhibitors. ICAAC (2001):Abs F387. Non β-lactam methylphosphonate irreversible inhibitors with specific activity against class A and class C β-lactamases. In vitro synergy was seen with penicillins and cephalosporins, and cephalosporins, and, more importantly, in vivo synergy with ceftriaxone was observed in a murine sepsis model.
53. Doran JL, Leskiw BK, Aippersbach S, Jensen S, Jensen SE: Isolation and characterization of a β-lactamase-inhibitory protein from Streptomyces clavuligerus and cloning and analysis of the corresponding gene. J Bacteriol (1990) 172:4909-4918.
54. Rudgers GW, Huang W, Palzkill T: Binding properties of a peptide derived from β-lactamase inhibitory protein. Antimicrob Agents Chemother (2001) 45:3279-3286.
55. Toney JH, Hammond GG, Fitzgerald PM, Sharma N, Balkovec JM, Rouen GP,Hammond ML, Greenlee ML, Gao YD: Succinic acids as potent inhibitors of plasmid-borne IMP-1 metallo-β-lactamase. J Biol Chem (2001): 276:31913-31918.
56. Concha NO, Janson CA, Rowling P, Pearson S, Cheever CA, Clarke BP, Lewis C, Galleni M, Frere JM, Payne DJ, Bateson JH, Abdel-Meguid SS: Crystal structure of the IMP-1 metallo-β-lactamase from Pseudomonas aeruginosa and its complex with a mercepatocarboxylate inhibitor: Binding determinants of a potent, broad-spectrum inhibitor. Biochemistry (2000) 39:4288-4298.
57. Mollard C, Moali C, Papamicael C, Damblon C, Vessilier S, Amicosante G, Schofield CJ, Galleni M, Frere JM, Roberts GC: Thiomandelic acid, a broad spectrum inhibitor of zinc β-lactamases: Kinetic and spectroscopic studies. J Biol Chem (2001) 276:45015-45023.
58. Huntley JJ, Scrofani SD, Osborne MJ, Wright PE, Dyson HJ: Dynamics of the metallo-β-lactamase from Bacteroides fragilis in the presence and absence of a tight-binding inhibitor. Biochemistry (2000) 39:13356-13364.
59. Chamberland S, Chan C, Blais J, Mathias M, Malouin F, Lee VJ: MC-02,479, a new cephalosporin with high affinity for PBP 2a and stability to staphylococcal β-lactamases. ICAAC (1997) 37:Abs F178.
60. Fujimura T, Yamano Y, Yodhida I, Yoshida T, Shimada J, Kuwahara S: S-3578, a new broad-spectrum cephalosporin: III. Characterization of antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). ICAAC (2001) 41:Abs F372.
61. Fung-Tomc JC, Clark J, Minassian B, Pucci M, Tsai Y.-H, Gradelski F, Lamb L, Medina I, Huczko E, Chaniewski S et al: In vitro and in vivo activities of a novel cephalosporin, BMS-247243, against methicillin-resistant and -susceptible staphylococci. Antimicrob Agents Chemother (2002) 46:971-976.
62. Hebeisen P, Heinze-Krauss I, Angehm P, Hohl P, Page MGP, Then RL: In vitro and in vivo properties of Ro 63-9141, a novel broad-spectrum cephalosporin with activity against methicillin-resistant staphylococci. Antimicrob Agents Chemother (2001) 45:825-836. A complete description of the preclinical in vitro susceptibility profile and in vivo efficacy models to support the development of a representative anti-MRSA cephalosporin BAL-9141 and its prodrug BAL-5788. β-Lactamase stability data and PBP profiles included.
63. Kernodle DS, Stratton CW, McMurray LW, Chipley JR, McGraw PA: Differentiation of β-lactamase variants of Staphylococcus aureus by substrate hydrolysis profiles. J Infect Dis (1989) 159:103-108.
64. Chamberland S, Blais J, Hoang M, Dinh C, Cotter D, Bond E, Gannon C, Park C, Malouin F, Dudley MN: In vitro activities of RWJ-54428 (MC-02,479) against multiresistant Gram-positive bacteria. Antimicrob Agents Chemother (2001) 45:1422-1430.
65. Johnson AP, Warner M, Carter M, Livermore DM: In vitro activity of cephalosporin RWJ-54428 (MC-02479) against multidrug-resistant Gram-positive cocci. Antimicrob Agents Chemother (2002) 46:321-326.
66. Nishitani Y, Miwa H, Yoshida T, Shimada J, Kuwahara S: S-3578, a new broad-spectrum cephalosporin: I. Synthesis and structure-activity relationships. ICAAC (2001) 41:Abs F370.
67. Yamano Y, Miwa H, Motokawa K, Yoshida T, Shimada J, Kuwahara S: S-3578, a new broad-spectrum cephalosporin: II. In vitro activity against Gram-positive and -negative clinical isolates including methicillin-resistant Staphylococcus aureus (MRSA). ICAAC (2001) 41:Abs F371.
68. Blais J, Malouin F, Mathias K, Chan C, Chamberland S, Lee VJ: Bactericidal activity and post-antibiotic effect (PAE) of MC-02,479, a new cephalosporin with potent activity against multi-resistant Gram-positive bacteria. ICAAC (1997) 37:Abs F179.
69. Liu C, Corcoran C, Griffith D, Shen W, Sorensen K, Tembe V, Chen S, Clark D, Chambers HF et al: Efficacy of RWJ-54428 (MC-02,479) against methicillin-resistant Staphylococcus aureus (MRSA) endocarditis in the rabbit model. 37th Annual Meeting of the Infectious Diseases Society of America, PA, USA (1999):52.
70. Miwa H, Tsuji M, Yoshida T, Shimada J, Kuwahara S: S-3578, a new broad-spectrum cephalosporin: IV. Evaluation using experimental infection models with MRSA and/or Pseudomonas aeruginosa. ICAAC (2001) 41:Abs F373.
71. Entenza JM, Hohl P, Heinze-Krauss I, Glauser MP, Moreillon P: BAL9141, a novel extended-spectrum cephalosporin active against methicillin-resistant Staphylococcus aureus in treatment of experimental endocarditis. Antimicrob Agents Chemother (2002) 46:171-177.
72. Bush K: The evolution of β-lactamases. In Antibiotic Resistance: Origins, Evolution, Selection and Spread, Ciba Foundation Symposium. Chadwick DJ, Goode J (Eds), John Wiley & Sons, Chichester, UK (1997) 207:152-166.